Process of making aromatic isatin compounds.



UNITED STATES PATENT OFFICE.

RUDOLF KNIETSOH, ARTHUR HENRY STALAY HOLT, AND ERWIN OBERREIT, OF LUDWIGSHAFEN, GERMANY, ASSIGNORS TO THE BADISCHE ANILIN AND SODA FABRIK, OF SAME PLACE.

PROCESS OF MAKING AROMATIC ISATIN COMPOUNDS.

SPECIFICATION forming part of Letters Patent No. 646,841, dated April 3, 1900.

Application filed January 26,1899. Serial No. 703,504. (No specimens.) a

T aZZ whom it may concern.- homologues and analogues of these bodies,

Be it knownthat we, RUDOLF KNIETsCH, a yield isatin and its corresponding homo= subject of the King of Prussia, Emperor of logues and analogues on direct suitable oxi- Gerlnany, ARTHUR HENRY STALAY HOLT, a dation. This conversion into the isatin com- 5 subject of the Queen of Great Britain and Irepounds takes place directly without any preland, and ERWIN OBERREIT,a subject .of the vious conversion into nitroso or amido de- King of Saxony, all doctors of philosophy, and ri'vatives or any previous production or interresiding at Ludwigshafen-on-the-Rhine,in the mediate formation of indigo itself. The proc- Kingdom of Bavaria and Empire of Germany, ess is simple and gives very good yields. Al-

10 haveinvented new and useful Improvements most all the usual oxidizing agents can be in the Manufacture of Aromatic Isatin Oomused, and either acid, neutral, or alkaline sopounds, of which the following is a specificalution. Only such weak oxidizing agents tion. as ferric chlorid or oxygen cannot be used suc- WVe have invented a new process for the cessfully, because they result in the forma-- 15 manufacture of isatin, itshomologues, and tion of indigo itself. The oxidation can be its analogues of the aromatic series, any one efiected at the'ordinary temperature, but is or all of which we hereinafter designate by preferably carried out at temperatures from the term isatin bodies. to 100 centigrade.

Isatin has hitherto been prepared from a The following instances of the oxidizing 2o benzene derivative containing an aliphatic agents Which can successfully be employed side chain-as, for instance, nitro phenyl-prowill illustrate the wide choicethat there is in 70 piolic acid. (Berz'chte 13, p. 2259; 12, p. 350.) the oxidizing agents for use in this invention: Also isatin has been obtained from bodies (a) when oxidizing inacid solution,potassium containing the indol ring already formed. bichromate, lead nitrate, mercuric nitrate, or

25 Thus it is produced by the oxidation of indidilute nitric acid; (b) when oxidizingin neu= go-blue, of indigo-red, of indol, of oxy-indoltral solution, potassium permanganate under carboxylic acid,andof amido-oxy-indol. (See conditions when the solution is maintained Bem'chte 29, p. 658; 11, p. 1228.) neutral, for instance, by the addition of mag- Prior to our invention isatin has never been nesium sulfate; (c) when oxidizing in alka- 0 obtained from indoxylic acid and derivatives line solution, ammonium persulfate, potasthereof by direct oxidation. 7 sium chromate, manganic oxidizers, such as As is well known, if indoxyl or indoxylic potassium permanganate or manganese peracid be oxidized by the oxygen of the air in oxid, potassium ferricyanid, iodin, bromin,

alkaline solution indigo is produced, and the chlorin; ferric sulfate, cupric sulfate, or iner- 3 5 same is the case if an acid solution be oxicuric chlorid, precipitated with caustic soda dized by ferric chlorid. Therefore in case it lead peroxid. was desired to prepare isatin from indoxyl or The initial materials which have been sucindoxylic' acid or the like it was heretofore cessfully used areindoxyl and indoxylic acid, necessary either to oxidize these products to (or the melts containing the same or ana- 0 indigo and then prepare the isatin from this logues thereof, obtained in accordance with or to adopt some such indirect process as the the examples of Heumanns indigo patents;

conversion of the indoxyl into ethyl-indoxylic see, for instance, United States Letters Patent acid, nitrosing this body, and reducing the No. 534,560 and English Letters Patent Nos. nitroso-indoxyl thus obtained to the amido 8,726 and 10,509,0f 1890,) ethyl-indoxyl, acet- 45 compounds and oxidizing these. (See Berichte ylindoxyl, indoxylic ester, acetyl-indoxylic- 15, p. 7 84.) ester, (Berichzfe 14, p. 1742,)para-methyl-ind- The new process which we have invented is oxyl-ester, betanaphthindoxylic-ester, and based upon the fact that indoxyl, indoxylic the corresponding acids, all of which are hereacid, and their alkali derivatives, as also the inafter referred to as indoxyl compounds.

The following examples will serve to illustrate the manner in which the invention can best be carried into effect. The parts are by weight:

Example 1Oacidation of inclorylic acid with potassium, permanganate, and caustic soda-Prepare a solution of about six parts of potassium permanganate in fifty parts of water and containing ten parts of solid caustic soda. Heat this solution to about centigrade and add about seven parts of indoxylic acid. \Vhen the color of the permanganate disappears, filter from the precipitated manganese peroxid, neutralize the filtrate exactly, and evaporate down to a small volume. Then add an excess of hydrochloric or sulfuric acid and allow the isatin to crystallize out.

In the above example instead of seven parts of indoxylic acid rather more than eight parts of iudoxylic-ethyl-ester can be used and the reaction proceeds in a similar manner; or if the equivalent quantity of orthoor paramethyl-indoxylic-ester be used then the corresponding orthoor para-methyl-isatin results.

Example 2- OJ'ttttt/ttfll of naplitli imloxylieetliyl-ester with potassium ferricg anid and caustic sotla.Dissolve about eight parts of potassium ferricyanid in about one hundred and sixty parts of water and add about ten parts of caustic-soda lye, (containing about thirty-five per cent. NaOH.) Heat the solution to about centigrade and add gradually about two parts of naphthindoxyl-ethylester, (alpha or beta.) Stir while adding and continue stirring the mixture subsequently. After a short time the oxidation is concluded. Filter in order to separate from a small quantity of pitchy matter. Add hydrochloric acid to the filtrate. A deep-red crystalline precipitate of naphtisatin is obtained. Collect by filtration and work up in the usual way.

Emainple 3 Oxidation of indoa g l with manganese peroacid and caustic soda.Prepare a mixture of twenty parts regenerated manganese peroxid, thirty parts of water, and seven parts of caustic-soda lye, (containing about twenty per cent. NaOH.) Boil this mixture and add slowly an aqueous solution of eight parts of indoxyl. then the oxidation is completed, collect the isatin, as described in the foregoing Example 1.

Example 4O.ti(lati0n of inzloxylic acid 'itttlt cup'ric sulfate and caustic s0(la.Dissolve about four parts of crystallized copper sulfate in sixteen parts of boiling water and precipitate by adding about three parts caustic-soda lye, (containing about thirty-five per cent. NaOl'I.) Stircontinually and add about one part of indoxylic acid. The oxidation takes place almost immediately. Boil this mixture and filter off the precipitate of enprous oxid and add an excess of hydrochloric acid to the filtrate. The isatin will in a short time separate out in the crystalline form.

Exam 'ile 5-Owidatt0n of incloxylic acid with potassium ferrir'yam'il and caustic s0da.Dissolve about seven parts potassium ferricyanid in about two hundred parts of boilingwaterand add about ten parts of caustic-soda lye, (containing aboutthirty-five per cent. NaOH.) To this solution add gradually nine parts of indoxylic acid. The solution obtained contains the isatin.

Example 6-()0cidation of a melt containing indomylic acid with n it rte acitlr Preparc a mixture of three parts of nitric acid (containing about sixty-one per cent. HNO and one hundred parts of water. To this mixture sutficient acetic acid must be added to rather more than neutralize the alkali from the melt to be added with the indoxyl body, so that the oxidation liquid remains acid all the time while adding the melt. Add the meltgradually in the form of a fine powder, and continue adding this melt until a sample with drawn and rendered alkaline on treatment with air shows that there is a slight excess of indoxylic body present, in that indigo is formed. This indicates that the oxidation agent is used up. Neutralize the solution exactly with sodiu m carbonate, filter and concentrate by evaporation, and precipitate the isatin with sulfuric acid.

Now what we claim is l. The process for the production of an isatin body of thearomatic series by the direct oxidation of an indoxyl compound substantially as described.

2. The process for the production of an isatin body of the aromatic series by the direct energetic oxidation of the corresponding indoxyl compound, substantially as described.

The process of making an isatin body by direct energetic oxidation of the corresponding indoxylic-acid body, all substantially as described.

4. The process of making isatin by oxidation of indoxylic acid with a manganic oxidizer, all substantially as described.

In testimony whereof we have hereunto set our hands in the presence of two subscribing witnesses.

RLDOLF KNIETSCII. ARTHUR HENRY STALAY llOl/l. ERWIN OBERREI'I. Witnesses:

ERNEST F. EHRHARDT, HOWARD E. J. INGLEY. 

